Proteomic changes in Alzheimer's disease associated with progressive Aß plaque and tau tangle pathologies.
Nat Neurosci
; 27(10): 1880-1891, 2024 Oct.
Article
in En
| MEDLINE
| ID: mdl-39187705
ABSTRACT
Proteomics can shed light on the dynamic and multifaceted alterations in neurodegenerative disorders like Alzheimer's disease (AD). Combining radioligands measuring ß-amyloid (Aß) plaques and tau tangles with cerebrospinal fluid proteomics, we uncover molecular events mirroring different stages of AD pathology in living humans. We found 127 differentially abundant proteins (DAPs) across the AD spectrum. The strongest Aß-related proteins were mainly expressed in glial cells and included SMOC1 and ITGAM. A dozen proteins linked to ATP metabolism and preferentially expressed in neurons were independently associated with tau tangle load and tau accumulation. Only 20% of the DAPs were also altered in other neurodegenerative diseases, underscoring AD's distinct proteome. Two co-expression modules related, respectively, to protein metabolism and microglial immune response encompassed most DAPs, with opposing, staggered trajectories along the AD continuum. We unveil protein signatures associated with Aß and tau proteinopathy in vivo, offering insights into complex neural responses and potential biomarkers and therapeutics targeting different disease stages.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Amyloid beta-Peptides
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Neurofibrillary Tangles
/
Tau Proteins
/
Plaque, Amyloid
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Proteomics
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Alzheimer Disease
Limits:
Aged
/
Aged80
/
Female
/
Humans
/
Male
Language:
En
Journal:
Nat Neurosci
Journal subject:
NEUROLOGIA
Year:
2024
Document type:
Article
Affiliation country:
Sweden
Country of publication:
United States